For Healthcare Professionals

Study of ASTX295 in Patients With Solid Tumors With Wild-Type p53

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About the study

Study ASTX295-01 is a first in human Phase 1/2 open-label study of the safety, pharmacokinetics, and preliminary activity of ASTX295 in subjects with wild-type TP53 advanced solid tumors. Phase 1 is a dose escalation and dose expansion study design followed by a Phase 2 study.
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Who can take part

You may be eligible to participate in the study if you meet the following criteria:

INCLUSION CRITERIA

Age

  1. Participant must be 18 years of age or older, at the time of signing the informed consent. Type of Participant and Disease Characteristics
  2. Have histologically or cytologically confirmed advanced solid tumors that are metastatic or unresectable and are refractory or have relapsed after treatment with standard available therapies or for whom standard life-prolonging measures are not available.
  3. Phase 1: any tumor type is eligible
  4. Phase 2: eligible tumor types as follows: malignant pleural mesothelioma (MPM) (Cohort 1); Liposarcoma (well-differentiated (WD) , de
  5. differentiated (DD), or mix), intimal sarcoma, and other sarcomas with human murine double minute 2 (MDM2) amplification (Cohort 2); Glioblastoma multiforme (GBM) and tumors with CDNK2A loss of function (LOF) excluding MPM, liposarcoma, intimal sarcoma, and uveal melanoma (UVM) (Cohort 3); any solid tumors with molecular feature that may confer sensitivity to ASTX295 (Cohort 4); Uveal melanoma (Cohort 5); Any cancer type with MDM2 amplification excluding MPM, sarcoma, and UVM(Cohort 6).
  6. Documented wild-type TP53 and other molecular feature requirements.
  7. Have an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 2.
  8. Acceptable bone marrow function, as evidenced by the following laboratory data:
  9. Absolute neutrophil count (ANC) ≥1500 cells/mm3
  10. Platelet count ≥100,000 cells/mm3
  11. Hemoglobin >9 g/dL
  12. Adequate hepatic function as evidenced by:
  13. Serum total bilirubin ≤1.5 × upper limit of normal (ULN).
  14. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤ 3 ULN in the presence of liver metastases).
  15. Serum creatinine ≤1.5 × ULN OR calculated creatinine clearance (by the standard Cockcroft-Gault formula) of ≥50 mL/min or measured glomerular filtration rate of ≥50 mL/min. Sex
  16. Participant can be male or female Informed Consent
  17. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol, and willing to participate in the study. Participants are eligible to be included in Phase 1 Part B of the study only if all of the following additional criteria apply:
  18. In Phase 1 Part B (dose expansion) of the protocol, subjects must have disease lesions that are amenable to biopsy and must agree and be able to undergo a pre
  19. and on
  20. treatment biopsy. Participants are eligible to be included in Phase 2 of the study only if all of the following additional criteria apply:
  21. Have sufficient tumor specimen either from archival formalin-fixed, paraffin embedded (FFPE) tissue or tissue obtained by a fresh biopsy for analyzing TP53 at a central laboratory.
  22. Measurable disease according to appropriate criteria as per protocol.

EXCLUSION CRITERIA

Medical Conditions

  1. Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
  2. Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise subject safety, or the integrity of study outcomes, or interfere with the absorption or metabolism of ASTX295.
  3. History of, or at risk for, cardiac disease, as evidenced by any of the following conditions:
  4. Abnormal left ventricular ejection fraction.
  5. Congestive cardiac failure of ≥Grade 3.
  6. Unstable cardiac disease.
  7. History or evidence at Screening of long QT interval corrected for heart rate (QTcF), ventricular arrhythmias, clinically significant bradyarrhythmias, third-degree atrioventricular (AV) block, presence of cardiac pacemaker or defibrillator, or other clinically significant arrhythmias.
  8. Screening 12-lead electrocardiogram (ECG) with measurable QTcF interval of ≥470 msec. (Fridericia's formula should be used).
  9. Known advanced human immunodeficiency virus (HIV) infection (including AIDS): clinical stage ≥ 3 according to WHO classification and/or HIV-associated immunodeficiency.
  10. Known active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (Inactive Hepatitis Carrier and subjects with laboratory evidence of no active replication on antivirals
  11. viral load below limit of detection
  12. will be permitted).
  13. Known brain metastases, unless previously treated and clinically stable for at least 4 weeks with or without steroids.
  14. Known significant mental illness or other conditions, such as active alcohol or other substance abuse that, in the opinion of the investigator, predispose the subject to high risk of noncompliance with the protocol treatment or assessments. Prior/Concomitant Therapy
  15. Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX295), as follows:
  16. Cytotoxic chemotherapy within 3 weeks prior. Any encountered treatment-related toxicities (excepting alopecia) must be stabilized or resolved to ≤Grade 1.
  17. Monoclonal antibodies, biologics, or immunotherapy within 4 weeks prior. Any encountered treatment-related toxicities must be stabilized or resolved to ≤Grade
  18. Molecularly targeted drug or other investigational drugs, without the potential for delayed toxicity, within 4 weeks of the first dose of study treatment or 5 half-lives (minimum 14 days), whichever is shorter. Any encountered treatment-related toxicities must be stabilized or resolved to ≤Grade 1.
  19. Major surgery or radiation within 4 weeks prior to first dose (palliative radiotherapy to a single lesion within 2 weeks).
  20. Prior treatment with MDM2 antagonist
  21. Inability to swallow oral medication or inability or unwillingness to comply with the administration requirements related to ASTX295. Participants are excluded from the Phase 2 part of the study if any of the following additional criteria apply:
  22. Active malignancy other than the cancer under study (excludes low risk prostate cancer or early breast cancer with or without hormonal therapy, basal cell carcinoma of the skin and superficial bladder cancer).
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Study Locations

Enter your ZIP code/Postal code/PIN code to locate study sites near you:

How to Apply


Contact the study center to learn if this study is a good match for you.
Phone iconCall 925-560-0100Email iconEmail Study Center

Study’s details


Contition

Solid Tumor

Age

18+

Phase

Phase 1/Phase 2

Participants needed

250

Est. Completion Date

Aug 2025

Treatment type

Interventional


Sponsor

Astex Pharmaceuticals, Inc.

ClinicalTrials.gov identifier

NCT03975387

Study number

ASTX295-01

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